Protein interactions with HER-family receptors can have different characteristics depending on the hosting cell line

Pavel Barta, Jennie Malmberg, Ludmila Melicharova, John Strandgård, Anna Orlova, Vladimir Tolmachev, Milan Laznicek, Karl Andersson

Результат исследований: Материалы для журналаСтатьярецензирование

27 Цитирования (Scopus)

Аннотация

Cell lines are common model systems in the development of therapeutic proteins and in the research on cellular functions and dysfunctions. In this field, the protein interaction assay is a frequently used tool for assessing the adequacy of a protein for diagnostic and therapeutic purposes. In this study, we investigated the extent to which the interaction characteristics depend on the choice of cell line for HER-family receptors. The interaction characteristics of two therapeutic antibodies (trastuzumab and cetuximab) and one Affibody molecule (Z HER2:342), interacting with the intended receptor were characterized with high precision using an automated real-time interaction method, in different cell lines (HaCaT, A431, HEP-G2, SKOV3, PC3, DU-145). Clear differences in binding affinity and kinetics, up to one order of magnitude, were found for the interaction of the same protein binding to the same receptor on different cells for all three proteins. For HER-family receptors, it is therefore important to refer to the measured affinity for a protein-receptor interaction together with the hosting cell line. The ability to accurately measure affinity and kinetics of a protein-receptor interaction on cell lines of different origins may increase the understanding of underlying receptor biology, and impact the selection of candidates in the development of therapeutic or diagnostic agents.

Язык оригиналаАнглийский
Страницы (с-по)1677-1682
Число страниц6
ЖурналInternational Journal of Oncology
Том40
Номер выпуска5
DOI
СостояниеОпубликовано - мая 2012
Опубликовано для внешнего пользованияДа

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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